Helping HF patients feel better with iron

Source: Anker SD, et al. N Engl J Med 2009;361:2436-2448.

Globally defined, heart failure exists when delivery of oxygen to the tissues is insufficient to meet demand. Anything that compromises oxygen delivery or impairs blood oxygenation can only compound the situation. Accordingly, patients with chronic heart failure (CHF) who are anemic might understandably suffer greater symptom burden or limitations as a result.

Anker et al enrolled patients with CHF (n = 459) and iron deficiency as documented by a low ferritin level. Patients were randomized to receive either placebo or iron intravenously (as ferric carboxymaltose) and followed for 6 months. The primary outcomes of the trial were self-reported global assessment and NYHA functional class.

Iron was administered as a 4 mL bolus IV (200 mg iron) weekly until iron levels were restored (as measured by ferritin, hemoglobin, and transferrin saturation), and then monthly until the end of the trial.

At the end of the trial, both the global assessment and NYHA class were improved to a statistically significant degree more in the iron group than by placebo. There were no serious adverse reactions with the ferric carboxymaltose.

Previous smaller studies have generally had similarly favorable outcomes. Interestingly, both this trial and earlier trials have found that iron supplementation benefits CHF patients with or without anemia, suggesting that more study of the pathophysiologic role of iron in CHF is needed.

COPD and osteoporosis

Source: Ferguson GT, et al. Chest 2009;136:1456-1465.

Of the top 10 causes of death in America, COPD (fourth) might be likened to the Rodney Dangerfield of mortal maladies: "It don't get no respect." Our pulmonology colleagues like to remind us that in contrast to the other 9 top 10 mortal disorders — which are either improving or at least leveling off — COPD mortality is actually rising. One way to awaken clinicians' interest in COPD is to remind them that it's not just about the lungs: Patients with COPD suffer detriment in multiple tissue compartments, such as bone health.

The TORCH trial (Towards a Revolution in COPD Health) studied inhaled fluticasone, inhaled salmeterol, both, or placebo in more than 6000 subjects. A subgroup study (n = 658) looked at the effects on BMD in each treatment arm.

At baseline, more than half of both men and women with COPD had either osteoporosis or osteopenia. Although frank osteoporosis was more common in women (30% vs 18%), osteopenia was equal. This is a critically important observation, since most fractures happen in subjects with osteopenia not osteoporosis. (This is likened to the situation in hypertension: Even though the risk of severe HTN is greater, since there are so many more folks with stage 1 or stage 2 hypertension, most of the CV burden of HTN is not shouldered by folks with severe HTN).

The good news: There was no meaningful change in BMD related to inhaled steroids (alone or in combination with salmeterol). The bad news: Osteopenia and osteoporosis are frighteningly commonplace in COPD.

Secondary prevention of depression: Cognitive therapy

Source: Bockting CL, et al. J Clin Psychiatry 2009;70:1621-1628.

For mild-to-moderate depression, the literature indicates that cognitive therapy (COG) and pharmacotherapy have similar beneficial effects, although pharmacotherapy is often less expensive and may provide symptomatic improvement more quickly. Because depression is recurrent, it is important to identify whether long-term cognitive therapy is helpful to prevent such recurrences.

To investigate this issue, Bockting et al enrolled major depressive disorder patients who had achieved remission (n = 172) and compared usual care with usual care plus COG. The COG was administered as weekly 2-hour group sessions over a 2-month period. After this 2-month COG intervention, both groups were followed for 5.5 years.

The group that had received 8 weeks of COG had a 21% relative risk reduction for recurrence over the next 5 years. Suicide (60% of cases are related to depression) remains in the top 10 causes of death. The value of COG treatment for even as brief a period as 8 weeks might have substantial long-term clinical payoff.

Prediabetes treatment: A wealth of opportunity

Source: Rhee MK, et al. Diabetes Care 2010;33:49-54.

It is estimated that almost 40 million Americans have diabetes, and more than twice that many have prediabetes. Clinical trials from the United States and various other nations indicate that prediabetes progresses at a rate of 6%-10% each year to frank diabetes. Fortunately, the menu of interventions that forestall development of diabetes from prediabetes continues to expand. It now includes diet, exercise, metformin, thiazolidinediones, acarbose, and orlistat.

In the recent past, it has been suggested that persons with prediabetes merit pharmacotherapy with metformin (in addition to lifestyle) if they have both impaired fasting glucose and impaired glucose tolerance, and any one of: age > 60 years, BMI > 30 kg/m2, family history of diabetes, elevated triglycerides, reduced HDL, hypertension, or A1c > 6%.

Rhee et al invited employees of the Grady Health System, Emory HealthCare and University, and Morehouse School of Medicine to be screened for diabetes. Of the volunteers who qualified for glucose tolerance testing (n = 1581), the combination of factors sufficient to merit metformin treatment was 8.1%; an additional 4.6% of subjects were newly diagnosed as frankly diabetic. Now that firm indications for pharmacotherapy of prediabetes are established, clinicians have a wealth of opportunity for timely intervention.

Aspirin for primary prevention in diabetes? Maybe

Source: Calvin AD, et al. Diabetes Care 2009;32:2300-2306.

The syllogism seemed so simple: 1) The CV risk reduction of aspirin (ASA) in primary prevention is linearly related to baseline risk; 2) DM is a high-risk population for CV events; and 3) therefore, ASA should be really good for primary prevention in diabetics. Well, it's not quite so simple.

The authors of this report in Diabetes Care performed a random-effects meta-analysis and Bayesian logistic regression (whatever that means, you ask?) to provide an opinion about whether aspirin is beneficial for primary prevention in diabetes. Their conclusion, based upon 8 trials that included patients with diabetic subgroups among the overall cohort (5 trials) as well diabetes-only trials (3 trials), is that the benefits of aspirin are similar in persons with or without diabetes.

I don't really know what "a random-effects meta-analysis and Bayesian logistic regression" means, but it would appear encouraging that this analysis, which incorporates data from 8 major clinical trials totaling more than 90,000 study subjects suggests, that aspirin might be a good thing.

Trouble is, I'm just not so sure. First, it is a matter of debate whether there is really any such thing as primary prevention in diabetes; after all, adult type 2 diabetics are considered a CV risk equivalent, since their CV risk (without ever having an MI) is as great as a person who has already had one. So, is aspirin in a diabetic primary or secondary prevention?

Secondly, the only 2 recent trials that studied only diabetics and were primarily designed to study the effects of aspirin in diabetics (the JPAD and POPADAD trials) both failed to find a beneficial effect of aspirin.

For the time being, popular opinion suggests that aspirin is a good thing. I'm not so sure.

Dementia: No simple answer

Source: Snitz be, et al. JAMA 2009;302:2663-2670.

The burgeoning population of advanced seniors (age > 75 years) includes an ever-growing population of persons with cognitive impairment and dementia. Popular complementary and alternative interventions to forestall dementia abound, among which it has been suggested that ginkgo has memory-preserving qualities.

Unfortunately, the data supporting long-term favorable outcomes for cognitive function are lacking. Nonetheless, because Ginkgo biloba has a popular impression of being favorable for mental faculties, and because earlier trials have faced limitations of trial duration, size, and population age, more conclusive insights have been sought.

A study sample of community-dwelling seniors (n = 3069; mean age, 79 years) was administered either 120 mg of ginkgo or placebo twice daily for a median follow-up of 6.1 years. Rates of decline in cognitive function, and numerous other metrics including attention, language, executive function, and others, were not statistically improved by administration of ginkgo. Although there were no significant adverse effects attributable to ginkgo, there is no sound basis on which to advocate for long-term cognitive effects from ginkgo.